Optimal Antithrombotic Therapy in Ischemic Stroke Patients with Non-Valvular Atrial Fibrillation and Atherothrombosis

NCT03062319 | Terminated Phase 4 DMC

• 1 other identifier: ATIS-NVAF
• Study Type: interventional
• Target: 321
• Locations: 1 country
• Sites: 1

Brief Summary

The Purpose of this open-label randomized controlled multicenter trial is to evaluate the efficacy and safety of mono-drug therapy with oral anticoagulant compared to combination therapy with antiplatelet drug, in ischemic stroke patients with non-valvular atrial fibrillation and atherothrombosis.

Conditions

Ischemic Stroke; Atrial Fibrillation; Atherothrombosis

Keywords

anticoagulant; antiplatelet

Outcome Measures

Primary Outcomes (1)

• Composite endpoint of ischemic cardiovascular events and major bleeding

  One of the following ischemic cardiovascular events (cardiovascular death, ischemic stroke, myocardial infarction, systemic embolism, or ischemic events requiring urgent revascularization), or major bleeding defined by the International Society on Thrombosis and Haemostasis (ISTH) criteria

  2 years after randomization

Secondary Outcomes (7)

• All-cause mortality

  2 years after randomization

• Ischemic cardiovascular events

  2 years after randomization

• All ischemic cardiovascular events including transient ischemia

  2 years after randomization

• Ischemic stroke

  2 years after randomization

• Myocardial infarction and cardiovascular death

  2 years after randomization

Study Arms (2)

Dual-therapy group

ACTIVE COMPARATOR

Dual-therapy group: single anticoagulant drug and single antiplatelet drug. The dosage is determined according to each drug's package insert in Japan. In patients treated with warfarin, the target international normalized ratio (INR) range of 2.0-3.0 for those \<70 years and 1.6-2.6 for those =\>70 years is recommended according to the Japanese guidelines.

Drug: Oral Anticoagulant; Drug: Antiplatelet Drug

Single-therapy group

ACTIVE COMPARATOR

Single-therapy group: single anticoagulant drug. The dosage is determined according to each drug's package insert in Japan. In patients treated with warfarin, the target international normalized ratio (INR) range of 2.0-3.0 for those \<70 years and 1.6-2.6 for those =\>70 years is recommended according to the Japanese guidelines.

Drug: Oral Anticoagulant

Interventions

Oral Anticoagulant DRUG

warfarin, dabigatran, rivaroxaban, apixaban, or edoxaban

Dual-therapy group; Single-therapy group

Antiplatelet Drug DRUG

aspirin, clopidogrel, prasugrel, ticlopidine, or cilostazol

Dual-therapy group

Eligibility Criteria

• Age: 20 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Patients with an acute ischemic stroke or TIA from 8 days and up to 360 days from the onset of symptoms
• Age 20 or older
• Patients with non-valvular atrial fibrillation (chronic or paroxysmal) who start or continue taking an oral anticoagulant
• Patients who have one of the following atherothrombotic diseases
• A past history of ischemic heart disease (myocardial infarction, angina pectoris, coronary artery bypass graft (CABG), percutaneous coronary intervention (PCI)
• A past history of peripheral artery disease (symptomatic peripheral arterial occlusive disease, lower extremity bypass surgery/angioplasty/stenting)
• Carotid artery stenosis (symptomatic or asymptomatic (=\>50% diameter), a history of carotid artery stenting (CAS) or carotid endarterectomy (CEA))
• Intracranial artery stenosis (=\>50% stenosis of the diameter of a major intracranial artery: intracranial internal carotid artery, anterior cerebral artery (ACA)-A1 and A2, middle cerebral artery (MCA)-M1 and M2, posterior cerebral artery (PCA)-P1 and P2, vertebral artery, and basilar artery; a history of intracranial stent placement or intracranial bypass surgery)
• A past history of atherothrombotic brain infarction, lacunar infarction, or branch atheromatous disease
• Patients without severe disability (modified Rankin Scale score =\<4)
• Patients who can take oral medications
• Patients who can receive follow-up survey
• Provision of written informed consent either directly or by a suitable surrogate

You may not qualify if:

• History of myocardial infarction or acute coronary syndrome within the past 12 months
• Patients who underwent PCI with drug-eluting stents within the past 12 months or PCI with bare-metal stents within the past 3 months
• Patients who underwent carotid artery stent placement, intracranial stent placement, or lower extremity stent placement within the past 3 months
• History of symptomatic intracranial hemorrhage or gastrointestinal bleeding within the past 6 months
• Hemorrhagic diathesis or blood coagulation disorders
• Platelet counts \<100,000 /mm3 at enrollment.
• Severe anemia (hemoglobin \<7 g/dL)
• Severe renal failure (creatinine clearance =\<15 mL/min) or undergoing chronic hemodialysis.
• Severe liver dysfunction (Grade B or C of the Child-Pugh classification)
• Patients with severe disability requires constant nursing care, bedridden (modified Rankin Scale score =5)
• Pregnant or possibly pregnant women
• Active cancer
• Expectation of survival less than 2 years
• Anticoagulant or antiplatelet is scheduled to be discontinued for more than 4 weeks during the follow-up period
• Planned revascularization procedure during the follow-up period

Sponsors & Collaborators

• National Hospital Organization Osaka National Hospital: lead
• Network for Clinical Stroke Trials: collaborator
• The BMS/Pfizer Japan Thrombosis Investigator Initiated Research Program: collaborator

Study Sites (1)

National Hospital Organization Osaka National Hospital

Osaka, Osaka, 540-0006, Japan

Location

Related Publications (2)

• Okazaki S, Tanaka K, Yazawa Y, Doijiri R, Koga M, Ihara M, Yamamoto S, Kamiyama K, Honda Y, Uchida K, Yoshimoto T, Asakura K, Omae K, Tanaka K, Maeda H, Yamamoto H, Hirano T, Toyoda K, Iguchi Y, Noguchi T, Okada Y, Kitagawa K, Sakai N, Yamagami H; ATIS-NVAF Trial Investigators. Optimal Antithrombotics for Ischemic Stroke and Concurrent Atrial Fibrillation and Atherosclerosis: A Randomized Clinical Trial. JAMA Neurol. 2025 Dec 1;82(12):1227-1234. doi: 10.1001/jamaneurol.2025.3662.

  PMID: 41051787 DERIVED

• Okazaki S, Yamamoto H, Asakura K, Omae K, Maeda H, Tanaka K, Yamamoto S, Hirano T, Iguchi Y, Sakaguchi M, Koga M, Ihara M, Toyoda K, Noguchi T, Sakai N, Yamagami H. Optimal antithrombotic therapy in ischemic stroke patients with non-valvular atrial fibrillation and atherothrombosis: study protocol for a randomized controlled trial. Front Neurol. 2024 Oct 23;15:1468523. doi: 10.3389/fneur.2024.1468523. eCollection 2024.

  PMID: 39539664 DERIVED

MeSH Terms

Conditions

Ischemic Stroke; Atrial Fibrillation; Thrombosis

Interventions

Anticoagulants; Platelet Aggregation Inhibitors

Condition Hierarchy (Ancestors)

Stroke; Cerebrovascular Disorders; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Vascular Diseases; Cardiovascular Diseases; Arrhythmias, Cardiac; Heart Diseases; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Embolism and Thrombosis

Intervention Hierarchy (Ancestors)

Hematologic Agents; Therapeutic Uses; Pharmacologic Actions; Chemical Actions and Uses

Study Officials

• Hiroshi Yamagami, MD

  National Hospital Organization Osaka National Hospital

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: PREVENTION
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Director, Department of Stroke Neurology

Study Record Dates

• First Submitted: February 8, 2017
• First Posted: February 23, 2017
• Study Start: April 6, 2017
• Primary Completion: July 18, 2023
• Study Completion: July 18, 2023
• Last Updated: December 27, 2024

Record last verified: 2024-12

Locations

JP (1)